Farnesylation is a type of lipid modification involving the covalent addition of a farnesyl isoprenoid via a thioether linkage to cystine residues at or near the C-terminus of certain intracellular proteins. In the past several years farnesylation of proteins has been strongly linked to the onset of carcinogenesis attributable to the Ras oncogene. Farnesyl pyrophosphate (FPP) is utilized by the enzyme protein-farnesyl transferase (PFTase) as the source of this farnesyl moiety. We describe the design and synthesis of a farnesyl pyrophosphate analogue, 8-aniline-geranyl pyrophosphate (AGPP). We have replaced the _-terminal isoprene unit of FPP with an aniline functionality. The carbon isoprenoid chain of AGPP is nearly superimposable with FPP. AGPP is a substrate for PFTase and is as active as the natural substrate. We also describe the synthesis of 3H-AGPP via reductive amination using 3H-sodium acetoxyborotritide. 3H-AGPP is transferred to Ras by PFTase with the same kinetics as the natural substrate FPP. There is a AGPP concentration dependent appearance of 3H in the protein band that corresponds to the Ras protein on SDS-PAGE gel. AGPP or FPP, but not AGOH or farnesol can inhibit this concentration dependence. The Km value of the enzyme for AGPP compares favorably with that for FPP (0.13 _M). Studies will continue with tritiated AGPP and other photolabile analogs of FPP to elucidate the mechanisms of farnesylation and the early stages of carcinogenesis.